Glanzman’s Thrombosthenia – How listening to your patient is sometimes the simple key to good medicine

Case Report | DOI: https://doi.org/10.31579/2690-4861/013.

Glanzman’s Thrombosthenia – How listening to your patient is sometimes the simple key to good medicine

  • Thejus T Jayakrishnan MD 1*
  • Vladimir Limonnik DO 1
  • Deep Shah MD 1
  • Prerna Mewawalla MD 1
  • 1* Division of Hematology/ Medical Oncology, Department of Medicine, Allegheny General Hospital; Pittsburgh, PA.

*Corresponding Author: Thejus Jayakrishnan MD,Division of Hematology Oncology,Department of Medicine,320 E North Avenue, Pittsburgh.

Citation: Thejus T Jayakrishnan, Vladimir Limonnik, Deep Shah, Prerna Mewawalla. (2020) Glanzman’s Thrombosthenia – How listening to your patient is sometimes the simple key to good medicine. International Journal of Clinical Case Reports and Reviews. 2(3); DOI:10.31579/2690-4861/013

Copyright: © 2020 Thejus T Jayakrishnan, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 14 February 2020 | Accepted: 22 May 2020 | Published: 30 May 2020

Keywords: Clotting, Platelet, Genetics, Inherited disorders, Trauma, Transfusion

Abstract

Introduction

Glanzmann’s Thrombasthenia is a rare clotting disorder caused by impaired platelet function. Lack of awareness of the appropriate management of rare medical conditions may lead to patient dissatisfaction and potentially poor treatment outcome.

Case Report

A 78 year old male with a history of Glanzmann’s Thrombasthenia was admitted to the trauma service following a fall in which he sustained a facial laceration as well as maxillary sinus and nasal fractures. He received DDAVP 20 mcg and Tranexamic acid upon presentation to the emergency department (ED). In the ED, the patient requested administration of platelet transfusion, but was refused due to a normal platelet count. During the course of his hospital stay, he complained of epistaxis and was noted to have a downtrending hemoglobin from 11.0 g/dl to 9.0 g/dl. Patient and family were not comfortable when discharge plan was finalized and demanded platelet transfusion (due to history of needing platelets in association with injuries or procedures in the past) but was refused by the primary team as they continued to state that his platelet count is normal. On hospital day 3 hematology was consulted as patient and family were extremely angry and hematology recommended platelet transfusion. Further clinical information isn’t available as patient was transferred to another facility per family request as they wanted to be at a center which had the patient’s primary hematologist.

Discussion

A delay in specialist consultation resulted in patient dissatisfaction and extended the length of stay. Patients with rare medical conditions and potential for major complications should be managed aggressively with appropriate specialist consultation to promote patient satisfaction and improve overall quality of care. This case shows that as physicians it our duty to listen to our patient’s concerns and involve them in the medical decision making to provide optimal patient-centered care.

Introduction

Glanzmann’s Thrombasthenia (GT) is a rare clotting disorder caused by impaired platelet function [1]. It is caused by a defect and/or deficiency of a platelet integrin, alpha IIB beta 3. This integrin molecule serves as a receptor for fibrinogen and is essential for platelet aggregation in hemostasis [2]. Bleeding involving GT could be variable and sometimes severe [3]. Lack of awareness of the appropriate management may lead to patient dissatisfaction and potentially poor treatment outcome. We hereby outline such a case where delay in expert consultation resulted in a delay in treatment and adverse outcome namely patient dissatisfaction.

Case

A 78 year old male with a history of heart failure status post AICD/PPM, Coronary artery disease status post coronary artery bypass graft surgery x 4, percutaneous coronary artery stenting x 5, hypertension, hyperlipidemia, hepatitis C and importantly Glanzmann’s Thrombasthenia presented to the hospital after a fall.

Patient reported that he was closing heavy curtains at a rehabilitation facility when he lost his balance causing him to fall and strike the back of his head and right arm. He complained of diffuse pain all over his body especially his face from the fall. His heart rate was 75 beats per minute, blood pressure 150/90mm Hg and he had normal oxygen saturation on room air. Examination was positive for left frontal hematoma with significant periorbital swelling, right inner eye laceration with mild oozing, mild epistaxis with dried fresh blood in the posterior oropharynx, hematoma of right posterior forearm, tenderness to palpation of the abdomen, pelvis, Thoracic (T) and Lumbar (L) spine with no neurological deficits or peritoneal signs. Laboratory work up showed microcytic anemia with hemoglobin and hematocrit of 11g/dl and 34% with mean corpuscular volume of 81fl, and thrombocytopenia with platelet count of 141k/mcl. Computed Tomography (CT) scan revealed an acute fracture involving the right nasomaxillary suture extending into the frontal process of the right maxillary bone with possible involvement of nasolacrimal duct, possible left nasomaxillary fracture-diastasis, and fluid in the right mastoid air cells with no evidence of temporal bone fracture, sinus fracture and nasal fractures. CT of neck, CT T and L spine, CT Abdomen Pelvis were negative for acute fractures. He was evaluated by oral maxillofacial surgery team who performed bedside facial laceration repair. He was admitted to the trauma service for monitoring.

In the ED, the patient was concerned that he was swallowing blood and requested administration of platelet transfusion. In addition to the above laboratory work up he had a thromboelastography (TEG) that showed mild platelet dysfunction consistent with his history. He was given DDAVP 20 mcg and 1000 mg Tranexamic acid but refused platelet transfusion. During the course of his hospital stay, he complained of epistaxis and was noted to have down trending hemoglobin from 11.0 g/dl to 9.0 g/dl. Patient and family were not comfortable when discharge plan was finalized and demanded platelet transfusion (due to history of needing platelets in association with injuries or procedures in the past) but was refused by the primary team as they continued to state that his platelet count is normal. On hospital day 3 hematology was consulted as patient and family were extremely upset. Hematology recommended platelet transfusion and patient was transfused 2 units of platelets. Further clinical information is not available as patient was transferred to another facility per family request as they wanted to be at a center which had the patient’s primary hematologist.

Discussion

Glanzmann’s Thrombasthenia (GT) is a congenital clotting disorder first described by Dr. Eduard Glanzmann in 1918 as “hereditary hemorrhagic thrombasthenia” after patients were noted to have a prolonged bleeding time as well as the absence of platelet clumping on peripheral blood smear [4]. The prevalence of GT is estimated to be around one per million individuals in the general population [2]. However, highly consanguineous populations such as Iran, Canada, Newfoundland, and Jordan have an increased prevalence of approximately one per 200,000 individuals [5].

GT is characterized by the inability of platelets to form platelet-to-platelet aggregates and form a platelet plug at the site of blood vessel injury even with the release of physiologic agonists including collagen, thrombin, and adenosine diphosphate. This lack of aggregation is due to an abnormality in the surface adhesion complex glycoprotein (GP) IIb/IIIa receptor, an integrin made up of a heterodimer consisting of alpha IIb and beta3-subunits [6]. This integrin functions as a platelet fibrinogen receptor and is crucial for platelet aggregation and promoting hemostasis. Consequently, the lack of platelet aggregation and hemostasis ultimately leads patients suffering with this disorder to experience bleeding episodes. GT follows an autosomal recessive inheritance pattern and is due to a gene mutation of ITGA2B or ITGB3. These genes are located on chromosome 17q21 and are responsible for encoding the alpha IIb and beta3-subunits. A mutation in either of the two genes may lead to GT, however the patient must be homozygous for the same mutation or may be compound heterozygous for different mutations from each parent [3]. Although rare, GT may also be acquired and is due to autoantibodies developing against the glycoprotein (GP) IIb/IIIa receptor. This has been documented in individuals who have an underlying hematologic condition such as multiple myeloma and Hodgkin’s lymphoma [7].

Bleeding associated with GT ranges from mild to severe. The severity of bleeding and its association to specific GT mutations has not been well established. In one study, individuals with the α2 C807T gene polymorphism exhibited a milder clinical phenotype but it may not be of much clinical utility in genotyping these patients [8]. According to Glanzmann’s Thrombasthenia Registry (GTR) that prospectively studied 218 GT patients, the mean age at which a patient’s first bleeding symptoms occurred was around 5.6 years. Bleeding events were typically mucocutaneous and most commonly involved epistaxis (79.2%), gingival bleeding (61.9%), dental bleeding (37.6%), menorrhagia (73.6%), easy bruising/purpura/petechiae (43.1%), subcutaneous hematoma (37.6%), and gastrointestinal bleeding (22.9%) [9]. Patients presenting with these symptoms and in whom one suspects an underlying bleeding disorder should initially be evaluated regarding his or her personal and family history of bleeding and/or bruising. The patient should be questioned about the common manifestations of GT, including epistaxis, gingival bleeding and menorrhagia [2]. Bleeding assessment tools, such as that developed by the International Society for Thrombosis and Hemostasis, have been validated to objectively obtain a bleeding history [10]. Medications should be reviewed with particular attention to nonsteroidal anti-inflammatory drugs as these therapies are frequent causes for acquired platelet functional defects. Initial laboratory screening tests should include a complete blood count, peripheral blood smear, plasma thromboplastin time (aPTT), thrombin time (PT), fibrinogen level, Factor XIII screen, and Von-Willebrand disease studies, including VWF antigen, ristocetin cofactor activity, and Factor VIII activity [5]. If the history and screening tests are in favor of an inherited platelet defect, additional testing such as light transmission aggregometry (LTA) and flow cytometry may be utilized for definitive diagnosis. LTA is considered the gold standard test and will reveal absent response to all agonists except agglutination to ristocetin. Flow cytometry will reveal alpha IIb beta 3 integrin deficiency [11].

The management of GT is based on the severity of the bleeding. Patients with minor bleeding amenable to local control measures may be managed with pressure, ice packs, electrocauterization and surgical repair [2, 12]. Tranexamic acid which is an antifibrinolytic agent has also been utilized as a local hemostatic agent as in our case [5]. If the patients doesn’t respond appropriately to local hemostatic techniques or if the condition worsens, systemic measures may be pursued. The agents available for systemic management are evolving and include – platelets, antifibrinolytics, recombinant factor VIIa , either alone or in combination [9]. These agents are also used as prophylaxis during surgical procedures [9].

While the use of platelets have remained standard for both treatment of bleeding and as prophylaxis, the use of Factor VII either in isolation or in combination with other agents has been shown to be equally efficacious [9, 13]. It is especially effective in cases with platelet refractoriness such as in the presence of platelet antibodies [5, 14]. In addition to refractoriness, the risk of platelet transfusion also include infectious complications although the incidence may be very low [3]. Mechanism of action of Factor VII involves activation of Factor X resulting in burst of thrombin generation which in turn converts fibrinogen to fibrin and enhances GT platelet adhesion and aggregation. Thrombin also improves the stability of the final clot structure by different mechnanisms [3].

While the common presentations involve minor bleeding episodes – spontaneous or associated with procedures, major life threatening bleeds do occur in these patients [15]. There is no established guidelines for treating these patients and response to treatment is assessed through a combination of clinical assessment and funcitonal platelet testing [14, 15].  Therefore, care for patients who present with multi system trauma or require complex management is best coordinated in a multidisciplinary fashion involving expertise of hematoligists and transfusion medicine specialists in addition to the primary treatment team [5, 16]. As these patients are used prolonged bleeding and need for platelet transfusions, lack of timely transfusion in the setting of ongoing bleeding may be anxiety provoking for the patient and the family as in our case.

A delay in specialist consultation resulted in patient dissatisfaction and extended the length of stay. Patients with rare medical conditions and potential for major complications should be managed aggressively with appropriate specialist consultation to promote patient satisfaction and improve overall quality of care. This case shows that as physicians it our duty to listen to our patient’s concerns and involve them in the medical decision making to provide optimal patient-centered care.

Acknowledgment:

None

Prior presentations:

Pennsylvania Society of Oncology and Hematology, Pittsburgh, October 2019

Financial Disclosure:

None

Conflicts of Interest:

The other authors have no disclosures to make.There are no conflicts of interest

Informed Consent:

Informed consent was not obtained as no identifiable information is presented.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad